Process of preparing compounds of the 1-phenyl-2-amino-alcohols-1 series hydroxylated in the phenyl radical



Patented July 11, 1933 UNITED STATES PA EN )orricr.

MAX BocKivron GUSTAV EHRHART, ANn-LEoNnAnp-srnm, or FaAiwKronr-ou-rnn- MAIN, GERMANY, ASSIGNORS 'ro w n'rnaor CHEMICAL COMPANY, INC., on 'NEVI YORK, N. Y., A CORPORATION on NEW YORK rnoon ss'or rnnrnnme coMPoUNns on THE 1EHENYL 2-AMI1\To-Ai.c0no1;s-1

HYDROXYLATED IN THE PI-IENYL RADICAL N0 Drawing. Application filed June 2, 1931, Serial No Q 541,7 3 8,'- and. in Germany June 1 3, 1938..

The present invention relates to a process of preparing compounds of the l phenyl2- aminoalcohols-l series hydroxylated in the phenyl radical.

We have found that compounds of the 1.-

phenyl-Q-aminoalcohols-l series 'hydroxyiated in the phenyl radical of the following general formula nomonyomung .Y

wherein R stands for aphenyl radical substituted by at least one hydroxy group and Y for an alkyl group, are obtainable by causing hydroxylamine to act upon a compound of the following general formula son on .eoY

phatic-aromatic ketone, in which the hydroxy groups of the phenyl radical may be esterified or etherified, in an organic solvent,

as for instance alcohol.

The reduction of the oximes is preferably effected by a catalytic reduction process to which the compounds are subjected in the form of their salts or as free bases, preferably dissolved in an organic solvent, such as for instance alcohol. As catalysts may be used precious metal catalysts or other metal catalysts, for instance those of the iron group. The acyl, alkyl or aralkyl radicals by which the compounds may be substituted in the hydroxy groups of the phenyl nucleus, may be split off after the introduction of the oxime group at any stage of the process, forinstance, acyl radicals may be split ofi before tl einvention, but they are not intended to liniit it thereto. (l) 100' grams of meta-benzyloxybenzaldehyde are shaken for about 2 hours with 500 cc. of sodium bisulfite solution. The bisullite compound formed is filtered by suction and washed with alcohol and ether. I grams'of the bisulfite compound so obtained are then mixed with a solution of 35 grams of potassium cyanide in 350 cc. of water. The nitrile which then separates in the, form of an oil is taken up with other and dried by means ofsodium sulfate. After-distillationof the ether an oil is obtained which, after a short time, solidifies to a crystalline mass.

50 grams of meta-benzyloiiybenzaldehyde I cyanhydrin are dissolvedin 250 cc. of ether and gradually mixed, while well cooling,

with the calculated quantity of methyl magnesium iodide in ether. The reaction product is then mlXed with ice and the ether solution is separated. After drying by means of sodium sulfate and distilling'olf the ether, the keto-alcohol is obtainedin the form of a yellowish oil.

20 grams of the keto-alcohol obtained are mixed in absolute alcohol with the calculated quantity of hydroxylaminehydrochloride. After standing for several hours, the oXime obtained is isolated and hydrogenated in an alcoholic-hydrochloric acid solution with hydrogen in presenceof a palladium catalyst. The catalyst is separated by filtering by suction and the alcohol removed from the filtrate by distillation meta hydroxyphenylpropanola-minehydrochloride is obtained which, after recrystallization from propyl alcohol and ether, melts at 180 C. with decomposition.

(2) 20'grams of meta-benzyloxyphenylacetylcarbinol aredissolved in alcohol and hydrogenated at room temperature with by V Y drogen in presence of a palladium catalyst.

As soon as 1 molecular proportion of hydrogen has been absorbed, the reduction is interrupted. The catalyst is filtered by suction and the alcohol is distilled under reduced pressure. The 'meta-11ydroxyphenylacetyl carbinolis obtained in the form of a crystalline mass which is sufficiently pure for trans formation into the ox'ime in the'manne'r indicated in Example 1. By reducing the oxnne as indicated in Example 1 the meta-hydroxyphenylpropanolaminehydrochloride is obtained. I

(3) grams of the oXime of meta-benzyl- Q oxyphenylacetylcarbinol are dissolved in 250 cc. of alcohol and hydrogenated at80 (lwith hydrogen under a pressure of 40 atmospheres with dilute hydrochloric acid. On evaporation there is obtained the nieta-hydroxyphenylpropanolaminehydrochloride which,

after recrystallizing from propyl alcohol and ether, melts at 180 C. The yield amounts to 60% of the theory,

WVe claim: I 1. The process which comprises causing Y stands for an alkyl group,

hydroxylamine to act upon a compound of the following general formula wherein X stands for an aralkoxy group and and subjecting the oxirne thus obtained to a reduction process. i V

2. The process which comprises causing "hydroxylamine to act upon a compound of the following general formula demons I I and subjecting the oxime thus obtained to a reduction process by means of hydrogen in the presence of a catalyst.

. 3. The process which comprises causing hydroxylamine to act upon a compound of the following general formula I cn on '.oo;oH;

. I I y y ocn oam and subjecting the oxime thus obtained to a reduction process by means of' hydrogen in the presence of a palladium catalyst.

In testimony whereof, we aflix our signa- .L

elllOS.

MAX BooKMunL; GUSTAV EHRHART. IILEONHARD STEIN. 

